ObjectiveTo investigate the effects of Astragali Radix polysaccharides （APS） on the polarization of BV2 microglial cells in an oxygen-glucose deprivation/reoxygenation （OGD/R） model through regulation of the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsThe OGD/R injury model of BV2 microglia was established and divided into blank group， OGD/R group and APS group （0.4 g·L^-1 APS）. Neuroinflammatory injury was induced by lipopolysaccharide （LPS） and treated with APS. The cells were divided into blank group， LPS group （1 mg·L^-1 LPS） and APS group （0.4 g·L^-1 APS+1 mg·L^-1 LPS）. Cell viability was detected using the cell counting kit-8 （CCK-8） assay. Cell morphology was observed under an inverted microscope. Nitric oxide （NO） content in the cell supernatant was determined by the Griess assay. The secretion levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， IL-10， and IL-4 were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the double-positive rates of ionized calcium-binding adapter molecule-1/inducible nitric oxide synthase （Iba-1⁺/iNOS⁺） and ionized calcium-binding adapter molecule-1/arginase 1 （Iba-1⁺/Arg1⁺）， as well as the nuclear translocation rate of nuclear factor-κB p65 （NF-κB p65）. Protein expression levels of Iba-1， iNOS， Arg1， TLR4， and NF-κB p65 were detected by Western blot. ResultsIn the OGD/R injury model， compared with the blank control group， BV2 microglial cells in the OGD/R group were activated and exhibited amoeboid morphological changes. The secretion levels of NO， TNF-α， and IL-6 were significantly increased （P<0.01）. The double-positive expression rate of Iba-1⁺/iNOS⁺ and the protein expression of Iba-1 and iNOS were significantly increased （P<0.01）. The nuclear translocation rate of NF-κB p65 and the protein expression levels of TLR4 and NF-κB p65 were significantly increased （P<0.01）. The levels of IL-10 and IL-4 were significantly decreased （P<0.01）， and the double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the OGD/R group， the APS group （0.4 g·L^-1） showed reduced cell activation， significantly decreased secretion levels of NO， TNF-α， and IL-6 （P<0.01）， significantly decreased double-positive expression rate of Iba-1⁺/iNOS⁺ and relative protein expression of Iba-1 and iNOS （P<0.01）， significantly decreased nuclear translocation rate of NF-κB p65 and protein expression levels of TLR4 and NF-κB p65 （P<0.01）， significantly increased levels of IL-10 and IL-4 （P<0.01）， and significantly increased double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression （P<0.01）. In the LPS-induced neuroinflammation model， compared with the blank control group， the LPS group showed increased cell activation， significantly increased levels of NO， TNF-α， and IL-6， significantly increased Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the LPS group， the APS group showed reduced cell activation， significantly decreased levels of NO， TNF-α， and IL-6， Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly increased （P<0.01）. ConclusionAPS may reduce microglial activation and promote their polarization toward the M2 phenotype by inhibiting activation of the TLR4/NF-κB signaling pathway， thereby alleviating the neuroinflammatory response induced by OGD/R.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

BACKGROUND:At present,the incidence of scoliosis is increasing year by year,especially in adolescent idiopathic scoliosis.Therefore,it is more and more important to strengthen the research on the treatment of adolescent scoliosis. OBJECTIVE:To summarize the current status,hotspots,emerging trends,and frontiers of global research on the treatment of adolescent idiopathic scoliosis to provide reference and guidance for future related research. METHODS:The literature related to the treatment of adolescent idiopathic scoliosis was retrieved on the Web of Science Core Collection(WOSCC)database from 2013 to 2023.CiteSpace 6.2.R1 software was used for visual analysis of countries,institutions,authors,and keywords. RESULTS AND CONCLUSION:(1)A total of 561 English articles were included in this study.Among countries,institutions,and authors,the United States has contributed the most.Nanjing University and Qiu,Yong(Affiliated Drum Tower Hospital,Nanjing University School of Medicine)are the most published institution and author.The academic journal with the largest number of articles is the European Spine Journal.(2)In the analysis of cited literature,the top 10 most cited articles mainly describe the effects of surgical treatment and conservative treatment on improving adolescent idiopathic scoliosis,especially improving the curvature of patients.(3)Through the summary of highly cited articles and the keyword clustering,keyword prominence in-depth mining,the research hotspots are currently the relationship between Cobb angle and treatment choice,the therapeutic effect of exercise therapy and the therapeutic effect of posterior vertebral fusion.(4)The prognosis of patients with different curvatures has not been studied in depth,and the etiology of adolescent idiopathic scoliosis has not been clarified,so the relationship between curvature and prognosis and the etiology of adolescent idiopathic scoliosis may be a new research trend in the future.

Objective:To investigate the association between magnesium sulfate exposure within 24 h before birth and short-term outcomes in preterm infants under 34 weeks' gestation.Methods:This retrospective cohort study analyzed data from preterm infants under 34 weeks admitted to the neonatal intensive care unit of the Affiliated Hospital of Qingdao University between June 1, 2020, and December 31, 2024. Infants were categorized into the exposure and the control groups based on magnesium sulfate administration within 24 hours before delivery. Maternal characteristics, birth parameters, and neonatal outcomes were compared using independent t-tests or Chi square tests (Fisher's exact test), with logistic regression assessing magnesium sulfate's effect on non-cerebral palsy outcomes. Results:The cohort comprised 384 preterm infants (24-33 +6 weeks), with 290 (75.5%) in the exposure group and 94 (24.5%) in the control group. (1) Baseline characteristics showed no significant differences in maternal hypertensive disorders, antenatal corticosteroids administration, premature rupture of membranes, delivery mode, or male infant proportion (all P>0.05). The exposure group had lower birth weight [(1 583±451) vs. (1 744±473) g; t=2.97] and gestational age [(31.3±2.1) vs.(31.8±2.4) weeks; t=2.20; both P<0.05)]. (2) The exposure group demonstrated reduced incidence of in-hospital mortality [0.3% (1/290) vs. 6.4% (6/94); Fisher's exact test], grade Ⅲ-Ⅳ intracranial hemorrhage [1.7% (5/290) vs. 9.6% (9/94); χ2=12.86], and white matter injury [2.1% (6/290) vs. 9.1% (8/94); χ2=9.08] (all P<0.01). (3) Univariate logistic regression identified antenatal magnesium sulfate as protective against grade Ⅲ-Ⅳ intracranial hemorrhage ( OR=0.20, 95% CI: 0.04-0.96), white matter injury ( OR=0.11, 95% CI: 0.01-0.91), and in-hospital mortality ( OR=0.93, 95% CI: 0.88-0.99). (4) Multivariate analysis confirmed the independent protective effect of antenatal exposure of magnesium sulfate against intracranial hemorrhage in preterm infants under 34 weeks ( OR=0.19, 95% CI: 0.04-0.95), particularly pronounced in infants <32 weeks ( OR=0.11, 95% CI: 0.01-0.96). (5) No significant differences emerged in secondary outcomes including 5-minute Apgar scores, respiratory distress syndrome, surfactant administration, mechanical ventilation, bronchopulmonary dysplasia, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, early-onset sepsis, retinopathy of prematurity, metabolic bone disease, or hospitalization duration (all P>0.05). Conclusions:Magnesium sulfate exposure within 24 hours before delivery reduces grade Ⅲ-Ⅳ intracranial hemorrhage risk in preterm infants under 34 weeks, with enhanced protection in those <32 weeks, without increasing adverse effects in other organ systems.

Objective To construct a predictive model for the 3-year recurrence-free survival(RFS)after total endoscopic resection of early and mid-stage esophageal cancer,and to test it,in order to provide decision support for standardized management after total endoscopic resection of early and mid-stage esophageal cancer.Methods A retrospective study was conducted to include 306 patients with early-to-mid stage esophageal cancer who underwent total endoscopic resection in our hospital from January 2018 to December 2020.The patients were divided into a modeling set(n=204)and a validation set(n=102)according to a 2∶1 ratio.Univariate analysis and random forest algorithm were used to screen variables,and Cox regression analysis was used to analyze the factors affecting the 3-year RFS after total endoscopic resection for early-to-mid stage esophageal cancer.The R language was used to construct a nomogram prediction model for model validation,and the receiver operating characteristic curve(ROC curve)was drawn to calculate the area under the curve(AUC).The discrimination of the prediction model was evaluated,and the calibration curve and decision curve(DCA curve)were used to evaluate the predictive performance and clinical applicability of the prediction model.Results Among the 306 patients with early and mid-stage esophageal cancer who underwent total endoscopic resection,18 died 3 years after the operation,55 relapsed,233 achieved RFS,and the 3-year RFS rate was 76.14％.Through univariate and random forest algorithm screening,seven factors were identified as being associated with the RFS of patients three years after surgery.These factors were entered into a Cox regression analysis,and the results showed that positive abdominal lymph nodes,vascular cancer thrombus,clinical stage Ⅲ,gross type of erosion,age ≥ 65 years,and tumor diameter＞3 cm were risk factors for RFS three years after surgery(P＜0.05).Based on this,a nomogram prediction model for RFS three years after full endoscopic resection for early-to-mid stage esophageal cancer was constructed.Internal and external validation showed that the consistency index of the prediction model in the modeling set was 0.881,and the consistency index in the validation set was 0.867.The ROC curve validation showed that the AUC of the prediction model in the modeling set and validation set were 0.855(95％CI:0.778-0.932)and 0.826(95％CI:0.763-0.890),respectively.The DCA curve validation showed that the risk threshold of the modeling set and validation set were 0-0.95 and 0-0.77,respectively,when the model could achieve high net benefits.Conclusion The 3-year RFS after total endoscopic resection for early and middle stage esophageal cancer is related to multiple factors.The nomogram model based on clinical stage Ⅲ,positive abdominal lymph nodes,vascular tumor thrombus,and gross type of erosion has good clinical utility for predicting the 3-year RFS of patients after surgery,and is of guiding significance for medical staff in making decisions about the management of early and middle stage esophageal cancer after surgery.